sNDA for Darolutamide Plus ADT in mHSPC Submitted for FDA Review

Alicia Morgans, MD, MPH

A supplemental new drug application (sNDA) seeking expended indication for darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been submitted to the FDA, according to a press release from Bayer.¹

The submission of the sNDA is supported by positive findings from the phase 3 ARANOTE trial (NCT04736199), which evaluated the combination of the oral androgen receptor inhibitor in combination with ADT vs placebo plus ADT.

Findings from the trial were presented at the 2024 ESMO Congress and published in the Journal of Clinical Oncology. At the data cutoff of June 7, 2024, the darolutamide combination reduced the risk of radiographic progression or death by 46% compared with placebo plus ADT (HR, 0.54; 95% CI, 0.41-0.71; P < .0001), meeting the study’s primary end point. Radiologic progression-free survival (rPFS) rates at 24 months were 70.3% with darolutamide plus ADT and 52.1% with placebo plus ADT. The median rPFS was not reached (NR; 95% CI, NR-NR) vs 25.0 months (95% CI, 19.0-NR) with these respective combinations.²

Benefit with darolutamide plus ADT was observed across all secondary end points. Notably, overall survival (OS) data were immature at the time of the primary analysis.

No new safety signals were observed with the darolutamide combination. A low incidence of treatment-emergent adverse effects (AEs) was reported across arms, and similar proportions of grade 3 and 4 or grade 5 AEs were observed in both the experimental and control arms.

“Simply put, our ambition is to help more patients with prostate cancer,” Christine Roth, executive vice president of Global Product Strategy and Commercialization and member of the Pharmaceuticals Leadership Team at Bayer, stated in the press release.¹ “We are proud of the role NUBEQA currently plays in the treatment of mHSPC and with this FDA submission, hope to expand the use of NUBEQA to more patients with the disease, regardless of chemotherapy use.”

An Overview of the ARANOTE Trial

The randomized, double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of the combination in patients with mHSPC and an ECOG performance status between 0 to 2. Eligible patients were randomly assigned 2:1 to receive either darolutamide at 600 mg twice daily in combination with ADT (n = 446) or placebo in combination with ADT (n = 223).²

The study’s primary end point of rPFS was measured as time from randomization to the date of first documentation of radiological disease progression or death due to any cause. Overall survival (OS), time from randomization to the date of first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety all served as secondary end points .

Beyond ARANOTE: Ongoing Investigations of Darolutamide

In addition to the ARANOTE trial, darolutamide is currently being evaluated in several trials across genitourinary cancers.¹

The phase 3 ARASTEP trial (NCT05794906) is evaluating darolutamide in combination with ADT compared with ADT alone in patients with high-risk biochemical recurrence HSPC, no metastatic disease detected by conventional imaging, and a positive prostate-specific maturation antigen PET/CT scane at baseline. Additionally, the international phase 3 DASL-HiCaP study (ANZUP1801), led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group, is evaluating adjuvant darolutamide in localized prostate cancer with a high risk of recurrence.

Darolutamide is currently FDA approved in combination with docetaxel for the treatment of non-metastatic castration-resistant prostate cancer and mHSPC.

References

1. Bayer submits supplemental new drug application to U.S. FDA seeking expanded indication for NUBEQA® (darolutamide) in metastatic hormone-sensitive prostate cancer. News Release. Bayer. September 26, 2024. Accessed September 26, 2024. https://www.bayer.com/en/us/news-stories/expanded-indication-for-nubeqar
2. Saad F, Vjaters E, Shore ND, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial. Ann Oncol. 2024;35(suppl 2):1-72. doi:10.1016/annonc/annonc1623